S-1-based concomitant chemoradiotherapy for locally advanced non-small cell lung cancer: Two phase I trials from Okayama Lung Cancer Study Group (OLCSG)

Abstract

7547 Background: Chemoradiotherapy (CRT) is a standard treatment for unresectable locally advanced non-small cell lung cancer (LA-NSCLC), but the treatment outcomes have remained unsatisfied. Thus, more effective and feasible CRT is urgently needed to improve their survival. S-1 is a newly developed oral 5-fluorouracil derivative and has synergistic effects with radiation. However, the role of S-1 in CRT for LA-NSCLC has been undetermined. Methods: We conducted two phase I trials to define the maximum tolerated doses (MTDs) and dose-limiting toxicities (DLTs) of S-1-based chemotherapy when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) for LA-NSCLC. OLCSG 0501 was designed to evaluate the two cycles of combination of S-1 (days 1–14) and cisplatin (days 1 and 8) for patients aged 75 or younger. S-1/cisplatin dosages (mg/m2) were escalated as follows: 60/30, 60/40, 70/40, 80/40, and 80/50. The other trial, OLCSG 0502, recruited patients aged 76 or older and evaluated S-1 alone. S-1 dosages (mg/m2) were increased as follows: 60, 70, and 80. Results: A total of 44 previously untreated LA-NSCLC patients were enrolled (22 in both trials). The MTDs for S-1/cisplatin and S-1 alone were determined to be 80 mg/m2/day / 50 mg/m2 and 80 mg/m2/day, respectively. In the OLCSG 0501, DLTs included febrile neutropenia, thrombocytopenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced grade 3 or more acute radiation pneumonitis and only one patient experienced grade 3 radiation esophagitis. In the OLCSG 0502, the DLTs were febrile neutropenia, stomatitis and delayed second cycle of chemotherapy. The overall response rates in OLCSG 0501 and OLCSG 0502 were 86.4% and 59.1%, respectively. Conclusions: These results indicate that S-1-based concomitant CRT would be a feasible treatment option and further phase II trials are currently under way. No significant financial relationships to disclose.